Wilms' tumour gene 1 (WT1) as a target in curcumin treatment of pancreatic cancer cells

被引:35
作者
Glienke, Wolfgang [1 ]
Maute, Luise [1 ]
Wicht, Johannes [1 ]
Bergmann, Lothar [1 ]
机构
[1] Univ Frankfurt, Dept Med Hamatol Onkol 2, Univ Hosp, D-60590 Frankfurt, Germany
关键词
siRNA; WT1; Curcumin; Pancreatic cancer; LEUKEMIC-CELLS; SERINE PHOSPHORYLATION; INHIBITS PROLIFERATION; KAPPA-B; OVEREXPRESSION; EXPRESSION; GROWTH; STAT3; APOPTOSIS; BINDING;
D O I
10.1016/j.ejca.2008.12.030
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The transcription factor WT1 plays an important role in cellular proliferation and survival of various cancer cells, and is frequently expressed in pancreatic cancer. Curcumin has been shown to be a potentially effective agent in pancreatic cancer. In this context, the purpose of this study was to determine the role of WT1 in a curcumin-treated pancreatic cancer cell line. To study the effect of curcumin on the expression of WT1, we incubated the pancreatic cancer cell line PANC-1 with different amounts of curcumin. The expression of WT1 on mRNA and protein level was measured with real-time RT-PCR and Western blot analysis. The incubation of the pancreatic cancer cell line PANC-1 with curcumin resulted in an inhibition of cellular proliferation as measured with MTT assay. The expression of WT1 on mRNA and protein level was significantly down-regulated in a concentration-dependent manner after treatment with curcumin. The WT1 mRNA levels were decreased by 20%, 25%, 40%, 78% and 88% in response to 10, 20, 30, 40 and 50 mu M curcumin. The use of small inhibitory RNA (siRNA) targeting WT1 down-regulated the expression of WT1 about 90%. Combined treatment with curcumin and siRNA targeting WT1 resulted in a significant inhibition of cell proliferation compared to curcumin-treated cells alone. In conclusion, WT1 is involved in cellular proliferation of PANC-1 cells. Targeting WT1 gene expression with siRNA may enhance the efficacy of curcumin to inhibit cell proliferation. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:874 / 880
页数:7
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